tbuckley/cabot-search huggingface dataset:
Usage of immunotherapy in Merkel cell carcinoma from 2004 to 2016: A National Cancer Database (NCDB) analysis.
Authors: Michael Luka, Isaac Burright, Liam Townley, Peter T. Silberstein, Vincent Eaton
Journal: Journal of Clinical Oncology (2022)

e21576 Background: Merkel Cell Carcinoma (MCC) is a rare and aggressive skin malignancy with increasing incidence, likely due to an aging population. MCC has been shown to have an increased prevalence in immunosuppressed patients, and current clinical trials are investigating the potential for immunotherapy treatments. As the understanding of the underlying pathogenesis of MCC progresses, the ability to implement specific immunotherapy targets is being investigated and showing promise. Methods: Using the NCDB, we identified 6,918 patients diagnosed with Merkel Cell Carcinoma between 2004-2016 using ICD-O-3 histology code 8247. The cohort was analyzed to identify differences in survival outcomes among patients who received immunotherapy, chemotherapy, a combination of chemotherapy and immunotherapy, and neither chemotherapy nor immunotherapy. We performed univariate analysis to assess median length of survival for each of these specific treatment modality cohorts, in addition to descriptive statistics. Data were analyzed using SPSS and statistical significance was set at α = 0.05. Results: Between 2004 and 2016, 118 patients in the NCDB received immunotherapy. From 2004-14, 21 patients received immunotherapy (1.9 patients per year). The usage of immunotherapy increased drastically in 2015 and 2016 with 18 patients and 79 patients being treated with immunotherapy, respectively. Most immunotherapy patients (59%) received treatment at an academic research center while the remaining patients received immunotherapy at a comprehensive community cancer program (24.8%), an integrated cancer network (12%), or a community cancer program (4.3%). 41.7% of MCC immunotherapy patients were between 33 and 69 years of age, whereas 59.3% ranged from 70-90 years of age. Of the 118 MCC patients who received some form of immunotherapy, 39% had stage IV MCC, 38.1% had stage III MCC, 5.9% had stage II MCC, and 9.3% had stage I MCC. Conclusions: As the use of immunotherapy in MCC continues to rise, especially at academic research centers, future studies should investigate the trends of its usage, its effects on patient survival, and the stage of MCC in which immunotherapy is most often used. We found that patients that received both chemotherapy and immunotherapy had a significantly lower median survival than all other treatment combinations. We hypothesize that the poorer survival rates in the patients that received some form of immunotherapy is due to a later stage of treatment, but this will become clearer as the sample size of MCC patients receiving immunotherapy continues to grow.[Table: see text]
Association of HLA-DQ Heterodimer Residues −18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial–Type 1
Authors: Lue Ping Zhao, Jay Skyler, George K. Papadopoulos, Alberto Pugliese, James Antonio Najera, George P. Bondinas, Antonis K. Moustakas, Ruihan Wang, Chul-Woo Pyo, Wyatt C. Nelson, Daniel E. Geraghty, Åke Lernmark
Journal: Diabetes Care (2022)

The purpose was to test the hypothesis that the HLA-DQαβ heterodimer structure is related to the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).Next-generation targeted sequencing was used to genotype HLA-DQA1-B1 class II genes in 670 subjects in the Diabetes Prevention Trial-Type 1 (DPT-1). Coding sequences were translated into DQ α- and β-chain amino acid residues and used in hierarchically organized haplotype (HOH) association analysis to identify motifs associated with diabetes onset.The opposite diabetes risks were confirmed for HLA DQA1*03:01-B1*03:02 (hazard ratio [HR] 1.36; P = 2.01 ∗ 10-3) and DQA1*03:03-B1*03:01 (HR 0.62; P = 0.037). The HOH analysis uncovered residue -18β in the signal peptide and β57 in the β-chain to form six motifs. DQ*VA was associated with faster (HR 1.49; P = 6.36 ∗ 10-4) and DQ*AD with slower (HR 0.64; P = 0.020) progression to diabetes onset. VA/VA, representing DQA1*03:01-B1*03:02 (DQ8/8), had a greater HR of 1.98 (P = 2.80 ∗ 10-3). The DQ*VA motif was associated with both islet cell antibodies (P = 0.023) and insulin autoantibodies (IAAs) (P = 3.34 ∗ 10-3), while the DQ*AD motif was associated with a decreased IAA frequency (P = 0.015). Subjects with DQ*VA and DQ*AD experienced, respectively, increasing and decreasing trends of HbA1c levels throughout the follow-up.HLA-DQ structural motifs appear to modulate progression from islet autoimmunity to diabetes among at-risk relatives with islet autoantibodies. Residue -18β within the signal peptide may be related to levels of protein synthesis and β57 to stability of the peptide-DQab trimolecular complex.
LGG-02. Cardiac toxicity in patients receiving single-agent MEK inhibition
Authors: Evan Cantor, Margaret Shatara, Ashley Meyers, Andrea Ogle, Michele McHugh, Stephanie Reiners, Andrew Cluster, Mohamed S Abdelbaki, Pournima Navalkele, Nicole M Brossier
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: MEK inhibitor therapy is increasingly being utilized for the treatment of pediatric tumors, including low-grade glioma, plexiform neurofibroma and Langerhans cell histiocytosis. These drugs are well-tolerated but do have risk of toxicity, including cardiac toxicity. The purpose of this study is to better characterize MEK inhibitor-induced cardiac toxicity in pediatric patients. METHODS: Retrospective review of all patients who underwent MEK inhibitor mono-therapy for at least 3 months, 2015- 2021, age 25 years or less, at St. Louis Children’s hospital and Cardinal Glennon Children's hospital. RESULTS: We evaluated 31 patients, 19 (61%) with brain tumors and 12 (39%) without. Of the thirty-one, fifteen (48%) had NF1, 1 had Tuberous sclerosis. Cardiac toxicity consisted of asymptomatic sinus tachycardia, bradycardia, or decreased ejection fraction (EF). Thirteen patients (42%) experienced an asymptomatic decrease in left-ventricular ejection fraction (EF), Grade I-III. Time on therapy before decreased EF was 5 days to 21 months, median 2.8 months. Decreased EF developed in 5 of 13 patients receiving selumetinib and 8 of 18 receiving trametinib. Of the patients who developed decreased EF, 11 (85%) had brain tumors, 6 (46%) had NF1, and 89% had received prior systemic therapy. Out of the patients who had received no prior systemic therapy (6), 2 (33%) had decreased EF, while 11/25 (44%) of those who had received prior systemic therapy did. Drug was held temporarily for 6 patients, with dose limiting toxicity for 5 patients. Drug was discontinued for 1 patient after EF continued to decline despite dose reduction. Patients showed improvement in EF as early as 2 weeks after holding therapy. CONCLUSIONS: Cardiac toxicity in our patients was limited to asymptomatic reduction in ejection fraction, sinus bradycardia and tachycardia, reinforcing the need for appropriate monitoring via echocardiography. Prior systemic therapy was associated with decreased EF.
Disproportionate morbidity and mortality in African American and Asian patients from colorectal cancer: A nationwide analysis.
Authors: Jorge Franco, Diana Franco, Umer Farooq, Irene Ma
Journal: Journal of Clinical Oncology (2022)

3628 Background: Published literature points towards the disproportionate prevalence of colorectal cancer (CRC) in ethnic groups. Racial minorities are also prone to higher mortality due to inequalities in access to healthcare. Therefore, we examined the disparities in hospital-related outcomes among racial groups from CRC. Methods: We investigated the National Inpatient Sample 2019 employing International Classification of Diseases-10 (ICD-10) codes to include adult patients with CRC. We compared various outcomes stratified by racial groups with White as the reference group. Analyses were performed using STATA (v 14.2), considering 2 sided P&lt; 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student’s t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses and included: gender, Charlson Comorbidity Index, median household income for patients’ zip codes, hospital location/region/bedside, and insurance status. Results: Out of 732,492 included patients, 72.77% White, 13.66% African American (AA), 9.91% Hispanics, and 3.65% Asians were in the cohort. AA and Asians had higher mortality odds than White, while Hispanics had mortality similar to White. AA had a lower mean length of stay by 0.74 days than White. All racial groups incurred higher mean total charges compared to White. AA and Hispanics had lower odds of undergoing colectomy. Overall, all racial groups had high morbidity compared to White. Among subgroups, the odds of morbidity markers (sepsis, lower GI bleed, and acute renal failure) were higher in AA and Asians than Hispanics. Post-op adhesions and DVT/PE were not significantly different among racial groups. Conclusions: AA and Asians disproportionately suffer from higher mortality from colorectal cancer than Hispanics and White. Lower colectomy rates (a definitive CRC treatment) in AA and higher in-hospital complication burden in Asians are possible explanations; however, further research needs to establish if race-specific genomics are also responsible for disparities. [Table: see text]
Annual household income and its association with financial toxicity, health utility, and survival in head and neck cancer.
Authors: Christopher W Noel, Katrina Hueniken, David Forner, David Paul Goldstein, John R de Almeida
Journal: Journal of Clinical Oncology (2022)

e18040 Background: While several studies have documented a link between socioeconomic status and survival in head and neck cancer, nearly all have used ecologic, community-based measures. Studies using more granular patient level data are lacking. We sought to determine the association between baseline annual household income with financial toxicity, health utility and survival. Methods: This was a prospective cohort of adult head and neck cancer patients treated at tertiary cancer center between September 17, 2015, and December 19, 2019. Our primary exposure was annual household income at time of diagnosis. Outcomes of interest included disease-free survival, financial toxicity, measured using the FIT tool, and health utility, measured using the Health Utilities Index Mark 3. Cox proportional hazards models were used to estimate the relationship between household income and survival. Income was regressed onto log-transformed FIT scores using linear models. The association between income and health utility was explored using generalized linear models. A generalized estimating equations approach was incorporated to account for patient level clustering. Results: There were 555 patients included in this cohort. Two-year disease-free survival was worse for patients in the bottom income quartile (&lt; $30,000 - 67% [95%CI 58-78])) compared to the top quartile (≥$90,000 - 88% [95%CI 83-93]). In risk adjusted models, patients in the bottom income quartile had inferior disease-free survival (aHR 2.13 [95%CI 1.22-3.71]) but not overall survival (aHR 2.01 [95%CI 0.94-4.29]). The average FIT score was 22.6 in the lowest income quartile vs. 11.7 in the highest quartile. In adjusted analysis, low-income patients had 12-month FIT scores that were, on average, 134% higher (worse) [95%CI 16%-253%] than high-income patients. Similarly, health utility scores were, on average, 0.106 [95%CI 0.029-0.184] points lower for low-income patients. Conclusions: Head and neck cancer patients with a household income &lt; $30,000 experienced worse financial toxicity, health status and disease-free survival. Significant disparities exist for Ontario’s head and neck cancer patients.
Self-reported well-being of cancer survivor (CS)-caregivers: An analysis of the Behavioral Risk Factor Surveillance System (BRFSS).
Authors: Qian Wang, Changchuan Jiang, Hui Xie, Nicholas Theodoropoulos, Chi Wen, Yannan Li, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2022)

e22022 Background: With the advancement in cancer therapies and supportive care, the 5-year survival rate for all cancers combined has surpassed 67%, indicating an increased proportion of CS are going back to their life roles, including providing care to others. Being a caregiver is associated with an increased risk of physical and mental distress, depression, and sleep disturbance. Nevertheless, the well-being of “dual role” CS-caregivers remains unknown. Methods: Data were extracted from the BRFSS survey from 2016, 2018, and 2020. Outcome variables included self-reported poor general health, physical health, mental health, depression, physical inactivity, and inadequate sleep. Weighted multivariable logistic regression models were used to calculate the odds of self-reported well-being comparing CS-caregivers to non-CS caregivers. Results: 20% of CSs were caregivers. Among a total of 18,590 caregivers, 18,124 (weighted N=12,311,109) were non-CSs and 466 (weighted N= 287,807) were CSs. CS-caregivers were significantly more likely to have poorer general and physical health and be physically inactive than non-CS caregivers (Table). Differential impacts on the well-being of CS-caregiver were also observed by the female sex and less than 5 years since cancer diagnosis. Conclusions: One in five CS is a caregiver, translating into 3.4 million CS in the US population. CS-caregivers experience diminished well-being across a variety of measures than non-CS caregivers. These data suggest CS-caregivers may need additional psychosocial support. Future prospective longitudinal studies are needed to investigate the outcomes in this growing and vulnerable population.[Table: see text]
Analysis of prognostic factors and survival outcomes for patients with T1N0 HER2-positive infiltrating ductal carcinoma of the breast: A real-world study with long-term follow-up.
Authors: Song-lin Gao, Ding-yuan Wang, Xi Wang, Binghe Xu, Peng Yuan, Bo Zhang
Journal: Journal of Clinical Oncology (2022)

e12530 Background: The optimal adjuvant systemic treatment and prognostic factors for patients with T1N0 HER2-positive infiltrating ductal carcinoma (IDC) of the breast are still unclear. We conducted a real-world study in China to identify potential prognostic factors in this low-risk population, and to characterize survival outcomes of patients treated with different adjuvant strategies. Methods: We included patients with T1N0 HER2-positive IDC of the breast who were treated at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2010 to April 2017. We performed Cox multivariate analysis to identify potential prognostic factors for invasive disease-free survival (IDFS). We also compared survival outcomes of 1) patients treated with adjuvant chemotherapy alone, or chemotherapy plus trastuzumab (Chemo+T), or observation only; 2) patients receiving adjuvant anthracycline (AC)-based and non-AC regimens, both combined with trastuzumab. Inverse probability of treatment weighting (IPTW) propensity score was used to reduce the selection bias. Results: Overall, 692 consecutive patients with pT1N0 HER2-positive IDC of the breast were included. The median follow-up was 78.0 months. Cox multivariate analysis demonstrated that age≤40 (HR = 2.62, 95%CI 1.39-4.92, P = 0.003) and T1c (HR = 2.35, 95%CI 1.17-4.74, P = 0.017) were associated with inferior IDFS, whereas ER+PR+ (HR = 0.44, 95%CI 0.26-0.77, P = 0.004) and adjuvant trastuzumab (HR = 0.21, 95%CI 0.12-0.35, P&lt; 0.001) were associated with favorable IDFS. For adjuvant treatment, 104, 195, and 373 patients were identified for observation, chemotherapy alone, and Chemo+T, respectively. The IPTW-adjusted Kaplan-Meier analysis demonstrated that compared with observation and chemotherapy alone, the IDFS was significantly longer in the Chemo+T group ( P = 0.034 and &lt; 0.001, respectively). Meanwhile, compared with observation, chemotherapy alone did not significantly prolong IDFS ( P = 0.424). For the comparison of AC-based vs. non-AC regimens, 141 patients were identified in the AC-based group and 227 in the non-AC group. The Kaplan-Meier analysis indicated that patients in both groups had similar IDFS ( P = 0.242). Conclusions: For patients with T1N0 HER2-positive IDC of breast, age≤40, T1c, ER+PR+, adjuvant trastuzumab are independent prognostic factors. We recommend adjuvant chemotherapy plus trastuzumab, especially for patients with T1c tumors. When used in combination with trastuzumab, non-AC regimens may have similar efficacy with AC-based regimens.
Analysis of Hospital-Level Readmission Rates and Variation in Adverse Events Among Patients With Pneumonia in the United States
Authors: Yun Wang, Noel Eldridge, Mark L. Metersky, David Rodrick, Constance Faniel, Sheila Eckenrode, Jasie Mathew, Deron H. Galusha, Anila Tasimi, Shih-Yieh Ho, Lisa Jaser, Andrea Peterson, Sharon-Lise T. Normand, Harlan M. Krumholz
Journal: JAMA Network Open (2022)

It is known that hospitalized patients who experience adverse events are at greater risk of readmission; however, it is unknown whether patients admitted to hospitals with higher risk-standardized readmission rates had a higher risk of in-hospital adverse events.To evaluate whether patients with pneumonia admitted to hospitals with higher risk-standardized readmission rates had a higher risk of adverse events.This cross-sectional study linked patient-level adverse events data from the Medicare Patient Safety Monitoring System (MPSMS), a randomly selected medical record abstracted database, to the hospital-level pneumonia-specific all-cause readmissions data from the Centers for Medicare & Medicaid Services. Patients with pneumonia discharged from July 1, 2010, through December 31, 2019, in the MPSMS data were included. Hospital performance on readmissions was determined by the risk-standardized 30-day all-cause readmission rate. Mixed-effects models were used to examine the association between adverse events and hospital performance on readmissions, adjusted for patient and hospital characteristics. Analysis was completed from October 2019 through July 2020 for data from 2010 to 2017 and from March through April 2022 for data from 2018 to 2019.Patients hospitalized for pneumonia.Adverse events were measured by the rate of occurrence of hospital-acquired events and the number of events per 1000 discharges.The sample included 46 047 patients with pneumonia, with a median (IQR) age of 71 (58-82) years, with 23 943 (52.0%) women, 5305 (11.5%) Black individuals, 37 763 (82.0%) White individuals, and 2979 (6.5%) individuals identifying as another race, across 2590 hospitals. The median hospital-specific risk-standardized readmission rate was 17.0% (95% CI, 16.3%-17.7%), the occurrence rate of adverse events was 2.6% (95% CI, 2.54%-2.65%), and the number of adverse events per 1000 discharges was 157.3 (95% CI, 152.3-162.5). An increase by 1 IQR in the readmission rate was associated with a relative 13% higher patient risk of adverse events (adjusted odds ratio, 1.13; 95% CI, 1.08-1.17) and 5.0 (95% CI, 2.8-7.2) more adverse events per 1000 discharges at the patient and hospital levels, respectively.Patients with pneumonia admitted to hospitals with high all-cause readmission rates were more likely to develop adverse events during the index hospitalization. This finding strengthens the evidence that readmission rates reflect the quality of hospital care for pneumonia.
New Treatment Options for Patients With Bladder Cancer
Authors: Thomas W. Flaig
Journal: Journal of the National Comprehensive Cancer Network (2022)

Bladder cancer is not rare—in men, it is the fourth most common cancer and the eighth leading cause of cancer-related death. The emergence of new systemic therapies, approval of PD-1 and PD-L1 inhibitors, and progress in the development of biomarkers have revolutionized the treatment of this urologic malignancy. The current NCCN Guidelines, which reflect the most up-to-date, evidence-based data relating to the evaluation and management of bladder cancer, support the incorporation of some of these novel therapeutics into clinical practice.
Machine learning based detection of pancreatic tumors using the Dxcover cancer platform.
Authors: Matthew Baker, Alexandra Sala, James Munro Cameron, Loren Christie, Justin Conn, David Palmer
Journal: Journal of Clinical Oncology (2022)

e16275 Background: Pancreatic cancer is the 7 th most deadly cancer worldwide with over 460,000 victims per year. In the current diagnostic pathway, carbohydrate antigen (CA) 19-9 serum test is the blood assessment used for detection of pancreatic cancer; although, with poor positive predictive values reported, it is not specific for pancreatic tumors as its levels can be raised in symptomatic patients with other benign comorbidities and/or because of other tumors in the surrounding area. Attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR) has demonstrated exceptional potential in human blood serum analysis for cancer diagnostics and its implementation in the clinical environment could represent a significant step forward in the early detection of pancreatic cancer. This proof-of-concept study aimed to investigate the use of the Dxcover cancer liquid biopsy as a novel approach for pancreatic cancer detection. Methods: The study was focused on the discrimination between both cancer (n = 100) versus healthy control samples (n = 100), and cancer (n = 35) versus symptomatic non-malignant control samples (n = 35) from patients with comorbidities and/or confounding diseases. Various machine learning algorithms were applied to discriminate between the classes: random forest (RF), partial least squares-discriminant analysis (PLS-DA) and support vector machine (SVM). Receiver operating characteristic (ROC) analysis was also employed to evaluate the classes’ degree of diagnostic separability. Permutation tests were performed for each classification in order to ensure their statistical significance. Results: Cancer (n = 100) and healthy control samples (n = 100) were distinguished with excellent results, achieving results up to a sensitivity of 91.0 %, specificity of 87.6 %, and accuracy of 89.3 % with PLS-DA. Moreover, an area under the curve (AUC) equal to 0.954 was obtained through ROC analysis. When discriminating between cancer (n = 35) and symptomatic control samples (n = 35), accuracy values were recorded in the range between 70.6 and 77.3 % with ROC analysis showing a balanced sensitivity and specificity over 75 % with an AUC of 0.844. Both discriminations were proven statistically significant. Conclusions: Pancreatic cancer detection in early stages would be key in improving prognosis and survival rates of patients, through targeted earlier surgery and treatments. The Dxcover cancer liquid biopsy could represent a powerful tool in the clinical environment as an easy-to-use, minimally invasive and reliable spectroscopic blood test for detection of pancreatic cancer.